Sirolimus in association with mycophenolate mofetil induction for the prevention of acute graft rejection in renal allograft recipients

Introduction. A previous trial in renal transplantation comparing sirolimus (rapamycin) to cyclosporine (CsA) ina triple-drug therapy regimen with aza thioprine and corticosteroids found that the incidence of acute rejection w as similar (approximately 40%) with a trend for better renal function with sirolimus. Methods. In 14 European centers, first cadaveric renal allograft recipients were randomized to receive sirolimus (n=40) or CsA (n=38) in an open-label design. All patients received corticosteroids and mycophenolate mofetil 2 g/day. Sirolimus and CsA were concentration controlled; trough levels of my cophenolic acid and prednisolone were also measured. Results. At 12 months, graft survival(92.5% sirolimus vs. 89.5% CsA), patie nt survival (97.5% sirolimus vs. 94.7% CsA), and the incidence of biopsy-pr oven acute rejection (27.5% sirolimus vs. 18.4% CsA) were not statistically different. The use of antibodies to treat suspected rejection episodes was also similar (7.5% sirolimus vs. 5.3% CsA). More sirolimus patients receiv ed bolus steroid therapy (20 vs. 11, P=0.068). From month 2 onward, the cal culated glomerular filtration rate was consistently higher in sirolimus-tre ated patients. The adverse events reported more frequently with sirolimus w ere thrombocytopenia (45% vs. 8%) and diarrhea (38% vs. 11%). In the CsA gr oup, increased creatinine (18% vs. 39%), hyperuricemia (3% vs. 18%), cytome galovirus infection (5% vs. 21%), and tremor (5% vs. 21%) were observed sig nificantly more often. Discussion. Patient and graft survival and the incidence of biopsy-proven a cute rejection at 12 months were comparable between sirolimus and CsA, wher eas safety profiles were different. These data suggest that sirolimus may b e used as primary therapy for the prevention of acute rejection.